Effect of cue-based feeding on time to nipple feed and time to discharge in very low birth weight infants

The objective of this study is to evaluate the effectiveness of a cue-based feeding protocol in improving time to nipple feed and time to discharge in very low birth weight infants in a Level III Neonatal Intensive Care Unit. Demographic, feeding, and discharge data were recorded and compared between the two cohorts. The pre-protocol cohort included infants born from August 2013 through April 2016 and the post-protocol cohort included infants born from January 2017 through December 2019. 272 infants were included in the pre-protocol cohort and 314 infants in the post-protocol cohort. Both cohorts were statistically comparable in gestational age, gender, race, birthweight, prenatal care, antenatal steroid use, and rates of maternal diabetes. There were statistically significant differences between the pre- versus post-protocol cohorts in median post-menstrual age (PMA) in days at first nipple feed (PO) (240 vs 238, p = 0.025), PMA in days at full PO (250 vs 247, p = 0.015), and length of stay in days (55 vs 48, p = 0.0113). Comparing each year in the post-protocol cohort, for each outcome measure, a similar trend was noted in 2017 and 2018, but not in 2019. In conclusion, the cue-based feeding protocol was associated with a decrease in the time to first PO, time to full nipple feeds, and the length of stay in very-low-birthweight infants.


Scientific Reports
| (2023) 13:9509 | https://doi.org/10.1038/s41598-023-36634-y www.nature.com/scientificreports/ Several NICUs started implementing cue-based feeding transition and studies were published regarding its effectiveness. Some earlier studies showed a reduction in time to PO and length of stay after implementing the cue-based protocol 12,13 . Evidence about cue-based feeding effectiveness is conflicting, as the studies included infants across various gestational ages, mostly moderately preterm and late preterm, who don't represent the most at-risk patients, and the feeding outcomes assessed are not uniform across the studies [14][15][16] .
A variety of approaches are used in hospitals to initiate cue-based feeding, and our unit adopted the one from the Ludwig et al. study 10 . This study aims to assess whether implementation of a cue-based feeding protocol is associated with reduced time to first PO feeds, full PO feeds, and length of NICU stay in very low birth weight (VLBW) infants at Regional One Health.

Methods
This study was approved by the Institutional Review Board at the University of Tennessee Health Science Center through an exempt process. Additionally, informed consent was waived by the Institutional Review Board at the University of Tennessee Health Science Center, as this is a retrospective study based on deidentified data from the Regional One Health patient database. All methods were performed in accordance with the relevant guidelines and regulations. This is a retrospective study including VLBW infants born at the Regional One Health NICU between August 2013 until December 2019. Infants with congenital anomalies, necrotizing enterocolitis, severe intraventricular hemorrhage (grade III and grade IV), and any other anomaly that could affect feeding were excluded. Infants were divided into two cohorts. The pre-protocol cohort (before implementing the cue-based feeding protocol) included infants born from August 2013 through April 2016. The post-protocol cohort (after implementing the cue-based feeding protocol) included infants born from January 2017 through December 2019. The primary objective of the study was to determine if change of practice to a cue-based feeding protocol was associated with improved time to first PO, time to full PO, and decreased length of stay in the NICU.
Data on variables of interest including gestational age (GA), birth weight (BW), gender, race, prenatal care, antenatal steroids, and maternal diabetes were collected. In addition, data on neonatal feeding outcome variables including the date at the first readiness score, date at first PO feeds, date at full PO feeds, and length of stay in the NICU were collected. Demographic and outcomes data were compared between the two cohorts.
The chi-squared test was used for nominal data, the Mann-Whitney test for continuous data between 2 groups, and the Kruskal-Wallis test for continuous data between more than two groups. The Man-Whitney and Kruskal-Wallis tests were used due to the skewed nature of the data. We considered a p value of less than 0.05 to be statistically significant. Data analysis involved the use of Graph Pad Prism (GraphPad Software ® San Diego, California, USA).

Ethics approval and consent to participate. This study was approved by the Institutional Review
Board at the University of Tennessee Health Science Center through an exempt process. Informed consent was waived by the Institutional Review Board at the University of Tennessee Health Science Center, as this was a retrospective study based on deidentified patient data.
Feeding outcomes of the pre-protocol cohort were compared to each year in the post-protocol cohort (Fig. 3).

Discussion
Our project showed a decrease in the time to first PO, time to full PO, and length of stay in VLBW infants in the NICU after the implementation of a cue-based feeding protocol. The findings of our study are in line with current evidence involving moderately preterm infants, in which every week earlier that oral feeding was initiated, there was an associated decrease in the PMA of independent oral feeding achievement by 5 days 17 . In a randomized controlled trial involving 29 infants (< 30 weeks GA), early introduction of oral feeding using a structured protocol for feeding progression improved the transition time from gavage to full PO feeds 18 . The decreased length of stay as observed in our study was similar to other studies that involved infants > 28 weeks and infants < 32 weeks 15,19 .
Cue-based feeding has shown to have positive effects on short-term health outcomes in infants, demonstrating greater weight gain, fewer oxygen desaturations, and decreased frequency of gavage feeding events 20 . Several quality improvement (QI) initiatives have been implemented in NICUs with emphasis on cue-based feeding, and a systematic review of the QI initiatives concluded that weight gain, time to full oral feedings, and hospital length of stay may be improved 21 . This approach also allows for early identification of infants at risk for a delay in the achievement of feeding independence in order to implement tailored and developmentally appropriate interventions to succeed in the PO feeding 22 .
This protocol has implications not just for providers in the NICU, as parents should be encouraged to participate in feeding when present. Feeding cues and techniques should be reinforced by bedside caregivers, and implementation of cue-based feeding can promote parental involvement in the feeding process for preterm infants 23 . Increased parental involvement will improve comfort and confidence of parents in caring for a premature infant in the NICU.
The cue-based protocol in our unit assesses both breastfeeding and bottle-feeding readiness. Breastfed infants were subsequently assessed with a breastfeeding quality score. Though there is a large emphasis on the benefits of breast milk in preterm infants, feeding at the breast is often overlooked in the NICU. First oral feed at the breast and breastfeeding subsequently have been shown to increase the duration of breastmilk feeding 24 . It will also help in preparing mothers for breastfeeding after discharge 25 .
Comorbidities in premature infants such as bronchopulmonary dysplasia (BPD), can prolong feeding readiness and initiation. based on their respiratory support requirements. There is inter-unit and inter-provider variation in starting PO in infants with BPD and on respiratory support. This is perceived as a barrier to the initiation and continuation of feeding protocols, along with the lower nurse-to-infant ratio. Our unit has established guidelines for infants on respiratory support for initiation of PO feeding. These guidelines have remained the same, along with the nurse-to-patient ratio, throughout both pre-and post-implementation.
Adverse events during feeding (desaturations below 85%, apnea > 20 s, and bradycardia) and unit-specific protocols on caffeine discontinuation can prolong the length of stay in preterm infants who can take all PO feeds. A decrease in the adverse events with cue-based feeding has been reported 12,26 . These events leading to a Table 1. Clinical characteristics of the study cohorts. Demographics of both cohorts. This data shows there were no statistically significant differences in basic demographics between the two groups. The results of the study encouraged the team to continue using the cue-based feeding protocol. Though encouraging results were observed in the first 2 years post-implementation, they were not sustained in the third year. This was concerning, and several factors, including lack of awareness and experience level of new caregivers, may have contributed. Increasing awareness of cue-based feeding effectiveness and implementing a structured continued education program regarding its use, implementing ongoing audits, and inclusion of parents may help sustain the improvement.

Pre-protocol (n = 272) Post-protocol (n = 314) p value
Timely identification of readiness to PO is important. Cue-based feeding protocols have shown to be helpful, along with skilled caregivers, to assist infants in creating a pleasurable feeding experience, minimizing stress, and maximizing intake 28 . This study adds to our understanding of the effectiveness of cue-based feeding protocols, particularly in VLBW infants. Our study, along with the existing evidence, will help make cue-based feeding a standard practice in the NICUs. This cue-based approach will help in process optimization and minimize variability, which will eventually help preterm infants attain feeding milestones appropriately and in a timely fashion.
The study is limited by being a single-center retrospective study, being unable to control for the level of training/experience of the caregivers when using the protocol. Changes in unit policy or processes that may have occurred between two cohorts might have impacted the feeding readiness and length of stay in NICU. Also, we were unable to analyze the outcomes separately in infants who were fed directly at the breast and by the bottle.